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PMID: 14673169 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Role for BRG1 in cell cycle control and tumor suppression.

Molecular and cellular biology ·Vol. 24 ·No. 1 ·2004-01-00 ·Pages 362-76

Hendricks KB, Shanahan F, Lees E

Abstract

Human BRG1, a subunit of the Swi/Snf chromatin remodeling apparatus, has been implicated in regulation of cellular proliferation and is a candidate tumor suppressor. Reintroduction of BRG1 into a breast tumor cell line, ALAB, carrying a defined mutation in the BRG1 gene, induced growth arrest. Gene expression data revealed that the arrest may in part be accounted for by down-regulation of select E2F target genes such as cyclin E, but more dramatically, by up-regulation of mRNAs for the cyclin-dependent kinase inhibitors p21 and p15. Protein levels of both p15 and p21 were induced, and p21 protein was recruited to a complex with cyclin-dependent kinase, CDK2, to inhibit its activity. BRG1 can associate with the p21 promoter in a p53-independent manner, suggesting that the induction of p21 by BRG1 may be direct. Further, using microarray and real-time PCR analysis we identified several novel BRG1-regulated genes. Our work provides further evidence for a role for BRG1 in the regulation of several genes involved in key steps in tumorigenesis and has revealed a potential mechanism for BRG1-induced growth arrest.

MeSH Terms
Adenoviridae Adenovirus E2 Proteins/metabolism CDC2-CDC28 Kinases/metabolism Cell Cycle/physiology Cyclin-Dependent Kinase 2 Cyclin-Dependent Kinase Inhibitor p21 Cyclins/metabolism DNA Helicases Gene Expression Profiling Gene Transfer Techniques Genes, Tumor Suppressor Genetic Vectors Humans Mutation Nuclear Proteins/genetics,metabolism Oligonucleotide Array Sequence Analysis Transcription Factors/genetics,metabolism
Chemicals
Adenovirus E2 Proteins CDKN1A protein, human Cyclin-Dependent Kinase Inhibitor p21 Cyclins Nuclear Proteins Transcription Factors CDC2-CDC28 Kinases CDK2 protein, human Cyclin-Dependent Kinase 2 SMARCA4 protein, human DNA Helicases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Hendricks Kristin B
DNAX Research Inc., Palo Alto, California 94304-1104, USA.
Shanahan Frances
Lees Emma
References (62)
62 references, click to expand
  1. Regulation of the human p21/WAF1/Cip1 promoter in hepatic cells by functional interactions between Sp1 and Smad family members.
    Proc Natl Acad Sci U S A. 1998 Jun 9;95(12):6733-8 PMID: 9618481
  2. p15INK4B is a potential effector of TGF-beta-induced cell cycle arrest.
    Nature. 1994 Sep 15;371(6494):257-61 PMID: 8078588
  3. Dissecting the regulatory circuitry of a eukaryotic genome.
    Cell. 1998 Nov 25;95(5):717-28 PMID: 9845373
  4. Altered control of cellular proliferation in the absence of mammalian brahma (SNF2alpha).
    EMBO J. 1998 Dec 1;17(23):6979-91 PMID: 9843504
  5. Intermediates in formation and activity of the RNA polymerase II preinitiation complex: holoenzyme recruitment and a postrecruitment role for the TATA box and TFIIB.
    Genes Dev. 1999 Jan 1;13(1):49-63 PMID: 9887099
  6. Germ-line and acquired mutations of INI1 in atypical teratoid and rhabdoid tumors.
    Cancer Res. 1999 Jan 1;59(1):74-9 PMID: 9892189
  7. Cyclin E associates with BAF155 and BRG1, components of the mammalian SWI-SNF complex, and alters the ability of BRG1 to induce growth arrest.
    Mol Cell Biol. 1999 Feb;19(2):1460-9 PMID: 9891079
  8. Cyclin D-CDK subunit arrangement is dependent on the availability of competing INK4 and p21 class inhibitors.
    Mol Cell Biol. 1999 Mar;19(3):1775-83 PMID: 10022865
  9. Transcriptional specificity of human SWI/SNF BRG1 and BRM chromatin remodeling complexes.
    Mol Cell. 2003 Feb;11(2):377-89 PMID: 12620226
  10. Loss of protooncogene c-Myc function impedes G1 phase progression both before and after the restriction point.
    Mol Biol Cell. 2003 Mar;14(3):823-35 PMID: 12631706
  11. Diverse gene sequences are overexpressed in werner syndrome fibroblasts undergoing premature replicative senescence.
    Mol Cell Biol. 1991 Aug;11(8):3905-14 PMID: 1712899
  12. Expression of CD44 is repressed in neuroblastoma cells.
    Mol Cell Biol. 1991 Nov;11(11):5446-53 PMID: 1922057
  13. A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia-telangiectasia.
    Cell. 1992 Nov 13;71(4):587-97 PMID: 1423616
  14. The retinoblastoma protein and BRG1 form a complex and cooperate to induce cell cycle arrest.
    Cell. 1994 Oct 7;79(1):119-30 PMID: 7923370
  15. The SWI-SNF complex: a chromatin remodeling machine?
    Trends Biochem Sci. 1995 Apr;20(4):143-6 PMID: 7770913
  16. Kip/Cip and Ink4 Cdk inhibitors cooperate to induce cell cycle arrest in response to TGF-beta.
    Genes Dev. 1995 Aug 1;9(15):1831-45 PMID: 7649471
  17. Transforming growth factor beta activates the promoter of cyclin-dependent kinase inhibitor p15INK4B through an Sp1 consensus site.
    J Biol Chem. 1995 Nov 10;270(45):26750-3 PMID: 7592908
  18. Expression of integrin alpha 3 in gastric and colorectal cancers: its relation to wall contraction and mode of invasion.
    Jpn J Cancer Res. 1995 Oct;86(10):934-40 PMID: 7493912
  19. Cell-specific induction of distinct oncogenes of the Jun family is responsible for differential regulation of collagenase gene expression by transforming growth factor-beta in fibroblasts and keratinocytes.
    J Biol Chem. 1996 May 3;271(18):10917-23 PMID: 8631909
  20. Functional interactions between the hBRM/hBRG1 transcriptional activators and the pRB family of proteins.
    Mol Cell Biol. 1996 Apr;16(4):1576-83 PMID: 8657132
  21. Diversity and specialization of mammalian SWI/SNF complexes.
    Genes Dev. 1996 Sep 1;10(17):2117-30 PMID: 8804307
  22. Complexes of adenovirus with polycationic polymers and cationic lipids increase the efficiency of gene transfer in vitro and in vivo.
    J Biol Chem. 1997 Mar 7;272(10):6479-89 PMID: 9045673
  23. SNF2beta-BRG1 is essential for the viability of F9 murine embryonal carcinoma cells.
    Mol Cell Biol. 1997 Oct;17(10):5976-86 PMID: 9315656
  24. Phenotypes of c-Myc-deficient rat fibroblasts isolated by targeted homologous recombination.
    Cell Growth Differ. 1997 Oct;8(10):1039-48 PMID: 9342182
  25. A simplified system for generating recombinant adenoviruses.
    Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2509-14 PMID: 9482916
  26. Differential preimplantation regulation of two mouse homologues of the yeast SWI2 protein.
    Dev Dyn. 1998 May;212(1):38-48 PMID: 9603422
  27. The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases.
    Cell. 1993 Nov 19;75(4):805-16 PMID: 8242751
  28. WAF1, a potential mediator of p53 tumor suppression.
    Cell. 1993 Nov 19;75(4):817-25 PMID: 8242752
  29. p21 is a universal inhibitor of cyclin kinases.
    Nature. 1993 Dec 16;366(6456):701-4 PMID: 8259214
  30. Perturbation of cell adhesion and microvilli formation by antisense oligonucleotides to ERM family members.
    J Cell Biol. 1994 Jun;125(6):1371-84 PMID: 8207064
  31. Human SWI-SNF component BRG1 represses transcription of the c-fos gene.
    Mol Cell Biol. 1999 Apr;19(4):2724-33 PMID: 10082538
  32. Transcriptional activation of the human S100A2 promoter by wild-type p53.
    FEBS Lett. 1999 Feb 26;445(2-3):265-8 PMID: 10094469
  33. Transforming growth factor beta1 acts as an inducer of matrix metalloproteinase expression and activity in human bone-metastasizing cancer cells.
    Clin Exp Metastasis. 1999 Feb;17(1):27-34 PMID: 10390144
  34. The mammalian SWI/SNF complex and the control of cell growth.
    Semin Cell Dev Biol. 1999 Apr;10(2):189-95 PMID: 10441072
  35. The "dark side" of chromatin remodeling: repressive effects on transcription.
    Cell. 1999 Nov 24;99(5):443-6 PMID: 10589670
  36. TGF-beta activates genes identified by differential mRNA display in pancreatic rudiments.
    Pflugers Arch. 2000;439(3 Suppl):R26-8 PMID: 10653130
  37. The E2F transcription factors: key regulators of cell proliferation.
    Biochim Biophys Acta. 2000 Feb 14;1470(1):M1-12 PMID: 10656985
  38. Exit from G1 and S phase of the cell cycle is regulated by repressor complexes containing HDAC-Rb-hSWI/SNF and Rb-hSWI/SNF.
    Cell. 2000 Mar 31;101(1):79-89 PMID: 10778858
  39. BRG-1 is required for RB-mediated cell cycle arrest.
    Proc Natl Acad Sci U S A. 2000 Jul 5;97(14):7748-53 PMID: 10884406
  40. The Swi/Snf family nucleosome-remodeling complexes and transcriptional control.
    Trends Genet. 2000 Aug;16(8):345-51 PMID: 10904263
  41. Role of Smad proteins and transcription factor Sp1 in p21(Waf1/Cip1) regulation by transforming growth factor-beta.
    J Biol Chem. 2000 Sep 22;275(38):29244-56 PMID: 10878024
  42. Smad2, Smad3 and Smad4 cooperate with Sp1 to induce p15(Ink4B) transcription in response to TGF-beta.
    EMBO J. 2000 Oct 2;19(19):5178-93 PMID: 11013220
  43. DRAL is a p53-responsive gene whose four and a half LIM domain protein product induces apoptosis.
    J Cell Biol. 2000 Oct 30;151(3):495-506 PMID: 11062252
  44. BRG1, a component of the SWI-SNF complex, is mutated in multiple human tumor cell lines.
    Cancer Res. 2000 Nov 1;60(21):6171-7 PMID: 11085541
  45. A Brg1 null mutation in the mouse reveals functional differences among mammalian SWI/SNF complexes.
    Mol Cell. 2000 Dec;6(6):1287-95 PMID: 11163203
  46. The BRG-1 subunit of the SWI/SNF complex regulates CD44 expression.
    J Biol Chem. 2001 Mar 23;276(12):9273-8 PMID: 11108719
  47. The murine SNF5/INI1 chromatin remodeling factor is essential for embryonic development and tumor suppression.
    EMBO Rep. 2000 Dec;1(6):500-6 PMID: 11263494
  48. S100A2, a putative tumor suppressor gene, regulates in vitro squamous cell carcinoma migration.
    Lab Invest. 2001 Apr;81(4):599-612 PMID: 11304580
  49. Identification of novel TGF-beta /Smad gene targets in dermal fibroblasts using a combined cDNA microarray/promoter transactivation approach.
    J Biol Chem. 2001 May 18;276(20):17058-62 PMID: 11279127
  50. Regulation of CSF1 promoter by the SWI/SNF-like BAF complex.
    Cell. 2001 Aug 10;106(3):309-18 PMID: 11509180
  51. Concomitant down-regulation of BRM and BRG1 in human tumor cell lines: differential effects on RB-mediated growth arrest vs CD44 expression.
    Oncogene. 2002 Feb 14;21(8):1196-207 PMID: 11850839
  52. Increased expression of pro-inflammatory cytokines and metalloproteinase-1 by TGF-beta1 in synovial fibroblasts from rheumatoid arthritis and normal individuals.
    Clin Exp Immunol. 2002 Mar;127(3):547-52 PMID: 11966774
  53. Microarray profile of differentially expressed genes in a monkey model of allergic asthma.
    Genome Biol. 2002;3(5):research0020 PMID: 12049661
  54. SWI/SNF complex interacts with tumor suppressor p53 and is necessary for the activation of p53-mediated transcription.
    J Biol Chem. 2002 Jun 21;277(25):22330-7 PMID: 11950834
  55. Expression of BRG1, a human SWI/SNF component, affects the organisation of actin filaments through the RhoA signalling pathway.
    J Cell Sci. 2002 Jul 1;115(Pt 13):2735-46 PMID: 12077364
  56. Loss of BRG1/BRM in human lung cancer cell lines and primary lung cancers: correlation with poor prognosis.
    Cancer Res. 2003 Feb 1;63(3):560-6 PMID: 12566296
  57. Molecular targets of the oncogenic transcription factor jun.
    Curr Cancer Drug Targets. 2003 Feb;3(1):41-55 PMID: 12570660
  58. ERM family members as molecular linkers between the cell surface glycoprotein CD44 and actin-based cytoskeletons.
    J Cell Biol. 1994 Jul;126(2):391-401 PMID: 7518464
  59. Cloning of p27Kip1, a cyclin-dependent kinase inhibitor and a potential mediator of extracellular antimitogenic signals.
    Cell. 1994 Jul 15;78(1):59-66 PMID: 8033212
  60. Changes in chromatin accessibility across the GM-CSF promoter upon T cell activation are dependent on nuclear factor kappaB proteins.
    J Exp Med. 2003 Feb 17;197(4):413-23 PMID: 12591900
  61. TGF-beta 1 stimulates expression of keratinocyte integrins during re-epithelialization of cutaneous wounds.
    J Invest Dermatol. 1994 Aug;103(2):221-7 PMID: 8040614
  62. Truncating mutations of hSNF5/INI1 in aggressive paediatric cancer.
    Nature. 1998 Jul 9;394(6689):203-6 PMID: 9671307
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.24.1.362-376.2004
Published
2004-01-00
Pages
362-76
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC303366
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.24.1.362-376.2004 PMC Full Text View journal details
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